Alginate hydrogel improves anti-angiogenic bevacizumab activity in cancer therapy

Alginate hydrogel improves anti-angiogenic bevacizumab activity in cancer therapyAnti-vascular endothelial growth factor (anti-VEGF) therapy applied to solid tumors is a promising strategy, yet, the challenge to deliver these agents at high drug concentrations together with the maintenance of therapeutic doses locally, at the tumor site, minimizes its benefits. To overcome these obstacles, we propose the development of a bevacizumab-loaded alginate hydrogel by electrostatic interactions to design a delivery system for controlled and anti-angiogenic therapy under tumor microenvironrnental conditions. The tridimensional hydrogel structure produced provides drug stability and a system able to be introduced as a flowable solution, stablishing a depot after local administration. Biological performance by the chick embryo chorioallantoic membrane (CAM) assay indicated a pH-independent improved anti-angiogenic activity (similar to 50%) compared to commercial available anti-VEGF drug. Moreover, there was a considerable regression in tumor size when treated with this system. Immunohistochemistry highlighted a reduced number and disorganization of microscopic blood vessels resulting from applied therapy. These results suggest that the developed hydrogel is a promising approach to create an innovative delivery system.that offers the possibility to treat different solid tumors by intratumoral administration.Brazilian Fundação de Amparo e Pesquisa do Estado de São Paulo (FAPESP), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). Additionally, this article has been developed under the scope of the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) Project PTDC/SAU-TOX/114549/2009 – FCOMP-01-0124-FEDER-016057, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-007038info:eu-repo/semantics/publishedVersio

March1-dependent modulation of donor MHC II on CD103+ dendritic cells mitigates alloimmunity.

In transplantation, donor dendritic cells (do-DCs) initiate the alloimmune response either by direct interaction with host T cells or by transferring intact donor MHC to host DCs. However, how do-DCs can be targeted for improving allograft survival is still unclear. Here we show CD103+ DCs are the major do-DC subset involved in the acute rejection of murine skin transplants. In the absence of CD103+ do-DCs, less donor MHC-II is carried to host lymph nodes, fewer allogenic T cells are primed and allograft survival is prolonged. Incubation of skin grafts with the anti-inflammatory mycobacterial protein DnaK reduces donor MHC-II on CD103+DCs and prolongs graft survival. This effect is mediated through IL-10-induced March1, which ubiquitinates and decreases MHC-II levels. Importantly, in vitro pre-treatment of human DCs with DnaK reduces their ability to prime alloreactive T cells. Our findings demonstrate a novel therapeutic approach to dampen alloimmunity by targeting donor MHC-II on CD103+DCs

Towards a new online species-information system for legumes

The need for scientists to exchange, share and organise data has resulted in a proliferation of biodiversity research-data portals over recent decades. These cyber-infrastructures have had a major impact on taxonomy and helped the discipline by allowing faster access to bibliographic information, biological and nomenclatural data, and specimen information. Several specialised portals aggregate particular data types for a large number of species, including legumes. Here, we argue that, despite access to such data-aggregation portals, a taxon-focused portal, curated by a community of researchers specialising on a particular taxonomic group and who have the interest, commitment, existing collaborative links, and knowledge necessary to ensure data quality, would be a useful resource in itself and make important contributions to more general data providers. Such an online species-information system focused on Leguminosae (Fabaceae) would serve useful functions in parallel to and different from international data-aggregation portals. We explore best practices for developing a legume-focused portal that would support data sharing, provide a better understanding of what data are available, missing, or erroneous, and, ultimately, facilitate cross-analyses and direct development of novel research. We present a history of legume-focused portals, survey existing data portals to evaluate what is available and which features are of most interest, and discuss how a legume-focused portal might be developed to respond to the needs of the legume-systematics research community and beyond. We propose taking full advantage of existing data sources, informatics tools and protocols to develop a scalable and interactive portal that will be used, contributed to, and fully supported by the legume-systematics community in the easiest manner possible

New segregates from the Neotropical genus Stryphnodendron (Leguminosae, Caesalpinioideae, mimosoid clade)

Non-monophyly is a prominent issue in mimosoid legumes, even in some of the less speciose genera such as the neotropical genus Stryphnodendron. This genus includes 35 species occurring from Nicaragua to Southern Brazil mostly in humid forests and savannas. Previous taxonomic studies of Stryphnodendron have highlighted morphologically distinct groups within the genus, recognized by differences on leaves (number of pinnae and size of leaflets), inflorescences (a simple or compound thyrse), and fruit types (legume, nucoid legume or follicle). Recent phylogenetic analyses have confirmed the non-monophyly of Stryphnodendron, supporting the recognition of three independent and morphologically well-delimited genera. Here we re-circumscribe Stryphnodendron and propose the two new genera Gwilymia and Naiadendron. In addition, we also provide an updated taxonomic account of the closely related genus Microlobius, including the proposal of a lectotype for the single species in the genus

Reconstruction Activities And First Results From The Thomson Scattering Diagnostic On The Tcabr Tokamak

An incoherent and infrared Thomson scattering diagnostic (ITS) was transferred from ISTTOK (Lisboa) and reconstructed on TCABR (S. Paulo). In the first phase of this international collaboration, the diagnostic uses a Neodymium:Glass laser with up to 10 Joules per laser pulse and a first generation polychromator with three pairs of interference filters and avalanche photodiodes. It measures 90° scattered radiation in a single volume of observation with a single laser pulse to obtain the instant plasma electron temperature. This paper reports the reconstruction activities already carried out and presents the first experimental results. These activities include: new data model performance, laser refurbishing, new laser delivery system, stray-light reduction in the vacuum vessel, new collection lens and relative diagnostic calibration. A long run of experiments with this diagnostic shows consistency and coherence with the other TCABR diagnostics and gives indications to be able to contribute effectively to the Alfven heating program of this tokamak. © 2010 IOP Publishing Ltd.227Alonso, M.P., Wilcock, P.D., Varandas, C.A.F., (1999) Rev. Sci. Inst., 70 (1), p. 783Alonso, M.P., Berni, L., Severo, J.H., Borges, F.O., Elizondo, J.I., MacHida, M., Varandas, C.A.F., Galvo, R.M.O., (2008) Plasma Fusion. Sci., 996, p. 192Alonso, M.P., Figueiredo, A.C.A., Berni, L.A., Varandas, C.A.F., (2008) Plas. Sci. IEEE Trans. Plasma Sci., 36 (4), p. 11094Bellintani, J.V., Elfimov, A.G., Elizondo, J.I., Fagundes, A.N., Fonseca, A.M.M., Galvo, R.M.O., Guidolin, L., MacHida, M., (2006), 875, p. 350Berni, L.A., Alonso, M.P., Oliveira, R.M., (2004) Rev. Sci. Inst., 75 (10), p. 388

Black hole thermodynamical entropy

As early as 1902, Gibbs pointed out that systems whose partition function diverges, e.g. gravitation, lie outside the validity of the Boltzmann-Gibbs (BG) theory. Consistently, since the pioneering Bekenstein-Hawking results, physically meaningful evidence (e.g., the holographic principle) has accumulated that the BG entropy $S_{BG}$ of a $(3+1)$ black hole is proportional to its area $L^2$ ($L$ being a characteristic linear length), and not to its volume $L^3$. Similarly it exists the \emph{area law}, so named because, for a wide class of strongly quantum-entangled $d$-dimensional systems, $S_{BG}$ is proportional to $\ln L$ if $d=1$, and to $L^{d-1}$ if $d>1$, instead of being proportional to $L^d$ ($d \ge 1$). These results violate the extensivity of the thermodynamical entropy of a $d$-dimensional system. This thermodynamical inconsistency disappears if we realize that the thermodynamical entropy of such nonstandard systems is \emph{not} to be identified with the BG {\it additive} entropy but with appropriately generalized {\it nonadditive} entropies. Indeed, the celebrated usefulness of the BG entropy is founded on hypothesis such as relatively weak probabilistic correlations (and their connections to ergodicity, which by no means can be assumed as a general rule of nature). Here we introduce a generalized entropy which, for the Schwarzschild black hole and the area law, can solve the thermodynamic puzzle.Comment: 7 pages, 2 figures. Accepted for publication in EPJ